Many commercial products are produced using chemical as well as biological processes. Pharmaceuticals, for example, are produced in commercial quantities using scaled-up reactors and other equipment. So-called biologics are drugs or other compounds that are produced or isolated from living entities such as cells or tissue. Biologics can be composed of proteins, nucleic acids, or complex combinations of these substances. They may even include living entities such as cells. In order to produce biologics on a commercial scale, sophisticated and expensive equipment is needed. In both pharmaceutical and biologics, for example, various processes need to occur before the final product is obtained. For example, in the case of biologics, cells may be grown in a growth chamber or the like and nutrients may need to be carefully modulated into the growth chamber. Waste products generated by cells may also have to be removed on a controlled basis from the fermentation chamber. As another example, biologic products produced by living cells or other organisms may need to be extracted and concentrated. This process may involve a variety of filtration and separation techniques.
Because there are a number of individual processes required to be produce the final product, various reactants, solutions, and washes are often pumped or otherwise transported to various subsystems using conduits and associated valves. These systems may be quite cumbersome and organizationally complex due to the large numbers of conduits, valves, sensors, and the like that may be needed in such systems. Not only are these systems visually complex (e.g., resembling spaghetti) they also include many components that are required to be sterilized between uses to avoid cross-contamination issues. Indeed, the case of drug and biologic preparation, the Federal Food and Drug Administration (FDA) is becoming increasingly strict on cleaning, sterilization or bio-burden reduction procedures that are required for drug and pharmaceutical preparations. This is particularly of a concern because many of these products are produced in batches which would require repeated cleaning, sterilization or bio-burden reduction activities on a variety of components.
During the manufacturing process of pharmaceuticals and biologics there often is a need to incorporate sensors into the manufacturing process so that process variables are monitored. For example, the process variables that need to be monitored may include temperature, pressure, pH, conductivity, flow rate, and the like. In conventional setups, sensors are placed directly along one or more points of the production process whereby the sensors themselves are inserted into the production stream where the sensor makes direct contact with the reactant or product stream. Still other sensors may be positioned on the exterior of the conduit or tubing and used to monitor conditions in a non-invasive manner. For example, ultrasonic flow measurement devices are known that can be affixed to the outside of tubing used in low-pressure applications such as heart-lung machines. For example, em-tec GmbH (Germany) sells a line of flowmeters that can be used to measure the flow rate in such extracorpeal systems. While such flow sensors may be used for low-pressure environments, these sensors are not suitable for high-pressure applications. For example, the conduit and/or sensor unit may burst or otherwise fail when exposed to expansion forces created during high-pressure applications. In addition, such flow sensors cannot be used with reinforced conduit as the braiding or reinforcement interferes with the flow measurement signals. Unfortunately, high-pressures (e.g., those above about 30 psi) are increasingly being used in manufacturing processes for pharmaceuticals and biologics.
While reinforced conduit or tubing may be used for high pressure applications, these solutions suffer from the limitation that the tubing or conduit cannot be configured with sharp bends or curves to the reinforced nature of the tubing. The use of reinforced conduit or tubing thus requires long sections of conduit so that bends can be accommodated. This makes the layout and designs large and unwieldy. Moreover, such designs leave large hold-up volumes in the tubing and conduit which can mean the loss of significant dollars in product or reagents. While unreinforced tubing and conduit may be used in some applications, when higher pressures are used, unreinforced tubing or conduit may fail or burst. Moreover, in many applications, the system needs to undergo a pressure or integrity test to ensure that the components will operate properly. During such testing procedures, which can be conducted at elevated pressures, unreinforced tubing may tend to torque, move, or balloon which disrupts operational parameters and results in inaccurate results. There thus is a need for flow sensing devices that can be incorporated into high fluid pressure process streams.